Dentomaxillofacial Radiology (2006) 35, 24-29
© 2006 British Institute of Radiology
doi: 10.1259/dmfr/96590988
Interpretation of scintigraphic findings of oral malignant tumours with a new scanning agent of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (Tc-99m-MIBI)
T Sato*,1,
Y Kawabata1,
Y Saigo2,
Y Iwashita1,
S Suenaga1,
H Indo1,
S Hamahira1,
K Kawano1,
T Nitta3,
Y Morita4,
HJ Majima1 and
K Sugihara3
1 Field of Oncology, Department of Maxillofacial Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan;
2 Division of Clinical Engineering, Kagoshima University Hospital, Kagoshima, Japan;
3 Field of Oral and Maxillofacial Rehabilitation, Department of Oral and Maxillofacial Diagnostic and Surgical Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan;
4 Department of Oral Radiology, Tsurumi University School of Dental Medicine, Tsurumi, Japan
*Correspondence to: Tsuyoshi Sato, Field of Oncology, Department of Maxillofacial Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan; E-mail: sato{at}denta.hal.kagoshima-u.ac.jp
Received 12 October 2004;
revised 5 April 2005;
accepted 14 June 2005
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Abstract
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Objectives: The purpose of this study was to investigate the usefulness of a new scanning agent of technetium-99m-hexakis-2-methoxy-isobutyl-isonitrile (Tc-99m-MIBI) for the diagnosis of malignant tumours of the head and neck.
Methods: Scintigraphy with Tc-99m-MIBI was performed in 19 patients with malignant tumours of the head and neck. Factors of the early and delayed static scans (hot, warm or cold uptake), the early and delayed retention indexes, the blood flow index and the tumour retention index were obtained from Tc-99m-MIBI scintigraphy. Tumour retention indexes were classified into three grades; slightly (>0.9), moderately (0.9–0.8) and severely (0.8>) decreased. Grade of tissue differentiation of tumour (well, moderately or poorly differentiated) and tumour size (T1
T4) were examined using the excised tumour. Scintigraphic indexes and tumour characteristics were compared.
Results: The early static scan and tumour size showed a correlation with the blood flow index. However, the delayed static scan did not show any relationship with blood flow index and tumour size. The tumour retention index had a tendency to decrease in malignant tumours, and showed a significant correlation with the grade of tissue differentiation of the tumour.
Conclusions: The tendency of the tumour retention index to decrease in Tc-99m-MIBI scintigraphy showed the malignancy of tumour and would be useful for the diagnosis of malignant tumours of the head and neck.
Keywords: scintigraphy;; Tc-99m-MIBI;; tumour retention index;; malignant tumour
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Introduction
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A variety of imaging techniques are routinely used to obtain information about lesions. However, most techniques provide mainly morphological information, and do not satisfy oral surgeons at the point of qualitative information of lesions. It should be helpful for oral surgeons if they could obtain qualitative information from imaging techniques pre-operatively. We have been evaluating Tc-99m-MIBI (hexakis-2-methoxyisobutylisonitrile) as a scintigraphic agent for the qualitative diagnosis of tumours of the head and neck. This scintigraphic agent has been widely used to evaluate the viability of the myocardium, and recently, accumulation of this agent in malignant tumours has been reported.1,2 However, there are few reports concerning availability of this agent in tumours of the head and neck. Previous reports have described that Tc-99m-MIBI showed a high accumulation in malignant tumour in the early phase, but a low accumulation in the late phase. The efflux from tumour cells of Tc-99m-MIBI once taken up was faster in high-grade malignant tumours than low-grade ones.3,4 This phenomenon is interesting because it is completely contrary to our results of Tl-201 scintigraphy.5,6
In the present study, we evaluated the usefulness of Tc-99m-MIBI scintigraphy for the diagnosis of malignant tumour of the head and neck.
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Materials and methods
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Nineteen patients with squamous cell carcinoma of the head and neck were used in this study. They were six patients with tumour of the maxilla, nine of the tongue, two of the oral floor and two of the mandible. They were nine females and ten males ranging in age from 25 years to 92 years (mean age was 65.8 years). Patients who had undergone radiotherapy or surgical excision of the primary tumour were excluded from the present study. Patient distribution regarding site and sex is shown in Table 1
. Tumour tissues excised surgically were processed with the usual procedure and diagnosed by pathologists histopathologically (well, moderate and poor differentiation). Tumour size was evaluated clinically according to the T-classification (T1, T2, T3 or T4).
Scintigraphy was performed before treatment by using an intravenous injection of 600 MBq per 2 ml of Tc-99m-MIBI. The two curves in Figure 1 showed the change of radioactive count in tumour and control regions (time activity curves). As shown in Figure 1, an early dynamic scan (for 5 min immediately after injection, A), an early static scan (10 min after injection, B), a delayed dynamic scan and a delayed static scan (approximately 2.5 h after injection, C and D) were carried out by using a Gamma View scintillation camera (Hitachi Co., Tokyo, Japan) with a low energy ultra-high resolution parallel hole collimator. The dynamic scans were performed with a patient in prone position beneath the camera. Five-second scans were obtained continuously for up to 5 min in each early and delayed dynamic scan. A single 5 s scan constituted a frame datum. Two regions of interest on each frame, covering both a tumour region and a contralateral symmetrical region (control region), were used to evaluate uptake of Tc-99m-MIBI in the tumour. The blood flow, early and delayed retention indexes of the tumour were calculated by using the results of the early and delayed dynamic scans. The blood flow index was the ratio of the total radioactive count of tumour to the total radioactive count of control in the early dynamic scan from 30 s to 120 s after the injection (Figure 1, F/E). The early retention index was the ratio of the total count of tumour to the total count of control in the early dynamic scan from 4 min to 5 min after the injection (Figure 1, H/G). The delayed retention index was the ratio of the total count of tumour to the total count of control in the delayed dynamic scan (Figure 1, J/I). Moreover, the ratio of the delayed retention index to the early retention index was calculated and we employed this ratio as the tumour retention index. These indexes were obtained with reference to results in the literature.5–8 Grades of tumour retention index were classified into 3 groups: slightly (>0.9), moderately (0.9–0.8) and severely (0.8>) decreased. Grades of uptake of Tc-99m-MIBI of the static scan in tumours were classified into three groups: hot, warm and cold.
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Figure 1 Two curves showing radioactive count of Tc-99m-MIBI after injection in tumour and control. (A) Early dynamic scan was performed for 5 min immediately after injection. (B) Early static scan was carried out 10 min after injection. (C) Delayed dynamic and (D) static scans were performed 2.5 h after injection. Blood flow index (F/E) was obtained from early dynamic scan from 30 s to 120 s after injection. Early retention index (H/G) was obtained from early dynamic scan from 4 min to 5 min after injection, and delayed retention index (J/I) was obtained from delayed dynamic scan 2.5 h after injection. Tumour retention index was calculated from early and delayed retention indexes
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Results
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Relationship of blood flow index with uptake in static scans
Table 2 shows the relationship between the blood flow index and the uptake of Tc-99m-MIBI. Blood flow indexes were classified into three groups with reference to our previous report about Tl-201 scintigraphy:5 poor group (<1.1), moderate group (1.11.3), and rich group (1.3<). In this study, blood flow indexes ranged from 1.0 to 1.5 with 17 patients (89.5%) being more than 1.1. In the early static scan of Tc-99m-MIBI scintigraphy, all patients of the rich blood flow index group showed hot uptake. Of the moderate blood flow index group, patients showed warm uptake (10 patients) or hot uptake (2 patients). Of the poor blood flow index group, patients showed cold uptake or warm uptake. On the other hand, in the delayed static scan of Tc-99m-MIBI scintigraphy, most patients showed a decrease of uptake in comparison with the early static scan. Of the rich blood flow index group, all patients showed a distinct decrease of uptake. Five patients moved from the hot uptake group in the early static scan to the warm uptake group (three patients) or the cold uptake group (two patients) in the delayed static scan. In the moderate blood flow index group, six of ten patients moved from the warm uptake group to the cold uptake group, and one patient moved from the hot uptake group to the cold uptake group. In the poor blood flow index group, one patient moved from the warm uptake group to the cold uptake group. These results indicate that the early uptake depends mainly on the blood flow, but there may be some other factors in the delayed uptake. Statistical analysis indicated that there was a significant correlation between the blood flow index and the degree of uptake in the early static scan (P=0.02). However, there was no significant correlation between the blood flow index and the degree of uptake in the delayed static scan.
Relationship of tumour size (T-classification) with blood flow index and the early static scan
Table 3 indicates the relationship among the tumour size, the blood flow index and the early static scan of Tc-99m-MIBI. Of the large-size tumour groups (T3 group and T4 group), patients were found in the moderate blood flow index group. On the other hand, half of the patients of the small-size tumour group (T1 group) belonged to the rich or moderate blood flow index group. In the early static scan of Tc-99m-MIBI scintigraphy, two patients of the small-size tumour group (T1 group) showed hot uptake and two showed warm uptake. None of the large-size tumour groups (T3 group and T4 group) showed hot uptake, but all patients showed warm uptake. A large part of the medium-size tumour group (T2 group) showed warm or hot uptake. Thus, there seemed to be no distinct relationship between tumour size and uptake grade in the early static scan. There was a statistical correlation between tumour size and blood flow index (P=0.10), although there seemed to be no correlation from the subjective impression. No significant correlation was found between tumour size and early static scan of Tc-99m-MIBI scintigraphy. These results indicate that the accumulation of the early static scan may not much depend upon the tumour size. Moreover, there is no relationship between the blood flow and the tumour size.
Tumour retention index of Tc-99m-MIBI scintigraphy
Table 4 reveals the tumour retention indexes of 19 patients, which varied widely. The tumour retention indexes in patients ranged from 1.1 to 3.1 in the early dynamic scan with mean ± SD of 1.6±0.59, from 1.0 to 2.9 in the delayed dynamic scan with mean ± SD of 1.3±0.47, and from 0.70 to 1.0 in the tumour retention index with mean ± SD of 0.85±0.0077. Most of the tumour retention indexes were under 1.0. The statistical analysis showed a significantly different distribution between the early and delayed retention indexes (Mann-Whitney test, P < 0.05). We could find a decreasing tendency of tumour retention indexes from the early dynamic scan to delayed dynamic scan in malignant tumours of the head and neck. The "percentage decreases" ranged from 0% to 30%, with average ± SD of 15±7.7%.
Relationship of tumour retention index to tissue differentiation
Table 5 shows the relationship between the tissue differentiation and the tumour retention index. In the well differentiation group, patients showed the tumour retention indexes of >0.9, 0.9–0.8 and <0.8 in 5, 2 and 0 patients, respectively. In moderate differentiation group, patients showed the tumour retention indexes of >0.9, 0.9–0.8 and <0.8 in 1, 4 and 3 patients, respectively. In poor differentiation group, patients showed the tumour retention indexes of >0.9, 0.9–0.8 and <0.8 in 0, 2 and 2 patients, respectively. Most patients in the moderate and poor tissue differentiation groups showed the decreasing of tumour retention index, and furthermore, there was a significant correlation between tumour retention index and tissue differentiation (P=0.10).
A patient who showed a decreased tumour retention index is presented in Figure 2. The patient was a 71-year-old man with poorly differentiated squamous cell carcinoma of the left tongue. The early static scan image of Tc-99m-MIBI scintigraphy showed hot uptake in the tumour region (Figure 2A, arrow). However, the uptake distinctly decreased in the delayed static scan (Figure 2B). The early and delayed retention indexes were 1.4 and 1.2, respectively. The tumour retention index was 0.86 (14% decrease) indicating the malignancy of tumour.
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Figure 2 A 71-year-old man with squamous cell carcinoma in the left tongue. Early static scan of Tc-99m-MIBI scintigraphy showing hot uptake in the tumour region (A, arrow). Uptake decreased in the delayed static scan (B)
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Discussion
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To distinguish malignant tumours from benign tumours in the head and neck, computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound have increasingly been used. As a result, the use of scintigraphy has declined for this purpose. Nevertheless, scintigraphy has an advantage of detecting the quality or viability of tumours because the accumulation of nuclear agents in tumours chiefly depends upon the tumour viability and the viability is generally high in malignant tumours.5,9 Ga-67 scintigraphy (gallium-67) has been widely used for 30 years10 and Tl-201 scintigraphy (thallium-201 chloride) was introduced about a decade ago11 in Japan. Recently, Tc-99m-MIBI scintigraphy has been introduced as a myocardial perfusion-imaging agent. Tc-99m-MIBI scintigraphy also shows a distinctly positive accumulation in malignant tumours.
Concerning Tl-201 scintigraphy, we evaluated the tumour retention index (uptake ratio of delayed dynamic scan to early dynamic scan) with respect to the relationship with the histopathological type and the grade of differentiation of tumours. We obtained interesting results that the retention index showed a remarkable increase from the early to delayed dynamic scans in malignant tumours. The increase of tumour retention index was larger in poorly differentiated tumours, and the tumour retention index clearly showed a decreasing tendency in benign tumours.5,6
On the other hand, Tc-99m-MIBI scintigraphy in this study showed a different finding from Tl-201 scintigraphy. A decreasing tendency of tumour retention index was clearly observed in malignant tumours. The difference between Tl-201 scintigraphy and Tc-99m-MIBI scintigraphy probably depends on the accumulation mechanism. The uptake mechanism of Tl-201 may depend on the activity of Na+/K+-ATPase.12,13 Tl+ has physiological effects very similar to K+ because it has an ion radius similar to K+. Malignant tumours contain a lot of K+ and tumour growth correlates closely with the activity of Na+/K+-ATPase. On the other hand, the uptake of Tc-99m-MIBI was reported to depend potentially on the mitochondria and plasma membrane potentials. In addition, a high-level expression of P-glycoprotein in the cell membrane causes an active efflux of Tc-99m-MIBI once taken up in tumour cells.13,14 This P-glycoprotein is well known as a protein that is closely connected with multidrug resistance, and the expression of P-glycoprotein is higher in malignant tumours than benign tumours.13
In this study, we evaluated 19 patients with squamous cell carcinoma with respect to blood flow index and tumour retention index. There was a statistical correlation between the blood flow index and Tc-99m-MIBI uptake in the early static scan. However, the uptake in the delayed static scan showed no correlation with the blood flow index. Most of the patients showed the decreased uptake from the early static scan to the delayed uptake scan in Table 2
. Therefore, we thought that there might be some other factors other than the blood flow, which related to the efflux of Tc-99m-MIBI from tumour cells.
As for the tumour size, the blood flow index showed a correlation with tumour size (P=0.10), but the uptake in the early static scan did not show any correlation. Tomura et al3 reported a slight correlation of tumour size with uptake of Tc-99m-MIBI scintigraphy, but Thompson et al15 found no correlation between tumour size and Tc-99m-MIBI uptake. Our results in Tc-99m-MIBI scintigraphy showed no correlation between the tumour size and the uptake. In this study, a patient of small size group (T1) showed the rich blood flow index and hot uptake of the early static scan. Thus, there might be a possibility to detect small-size tumours with Tc-99m-MIBI scintigraphy, although we need further evaluation.
We also evaluated the tumour retention index for the purpose of distinguishing malignant tumours from benign tumours. As for the tumour retention index, both Tomura et al3 and Taki et al4 reported a decreasing tendency of tumour retention index of malignant tumours in Tc-99m-MIBI scintigraphy. Tomura et al3 reported a 25.1% decrease on average, ranging from 4% to 42% in malignant tumours, and Taki et al4 showed 31.0% on average, ranging from 2% to 67%. In their results, the averages of retention indexes were 1.9 and 2.32 in the early scan, and 1.4 and 1.87 in the delayed scan, respectively. Our results (Table 4) in this study were similar to those of their results, and the retention indexes ranged from 1.1 to 3.1 (average =1.6) in the early scan and from 1.0 to 2.9 (average =1.3) in the delayed scan. The percentage decrease was 15% on average. Both our results and their results distinctly showed a decreasing tendency of tumour retention index in malignant tumours. This tendency was clearly different from Tl-201 scintigraphy.5,6 This decreasing tendency also showed a correlation with the grade of tissue differentiation of malignant tumour. We could use this tumour retention index for the purpose of detecting malignant tumours of the head and neck. There may be a possibility of detecting malignant tumours by using Tc-99m-MIBI scintigraphy, because of the facts that the blood flow is usually richer in malignant tumours than benign tumours,16 that most of patients with malignant tumours belonged to the moderate and rich blood flow index groups, that the tumour retention index is smaller in malignant tumour than benign tumour, and that the tumour retention index shows a correlation with the tissue differentiation.
We use both Tl-201 scintigraphy and Tc-99m-MIBI scintigraphy in examination of malignant tumours. Each scintigraphy gives us important information of tumours such as the tumour retention index, and it is helpful to presume the histopathological type or grade of differentiation of tumour, although there are some subjects unresolved, i.e. it is hard to distinguish tumours and inflammatory lesions. In the present study, we only evaluated the squamous cell carcinomas. However, Tc-99m-MIBI has been used for other types of malignant tumours: melanoma, osteosarcoma, malignant fibrous histiocytoma, malignant schwannoma, multiple myeloma, adenocarcinoma, non-Hodgkin's lymphoma and glioma.3,4 Out of these malignant tumours, Tomura et al3 reported that melanomas and adenocarcinomas showed a relatively distinct accumulation in comparison with squamous cell carcinomas. However, Taki et al4 reported that the accumulation showed a considerable variation in the same type of malignant tumours. Probably, there would be a difference of accumulation of the nuclear agent among the different types of malignant tumours. However, many factors, for example the histopathological type, the tumour vascularity, the grade of malignancy and the tumour viability, would cause the varied accumulation.5,6
In summary, we evaluated 19 patients with squamous cell carcinoma of the head and neck with Tc-99m-MIBI scintigraphy. We could obtain small retention indexes in patients with malignant tumour (average ± SD =0.85±0.0077) suggesting that Tc-99m-MIBI had a decreasing tendency in malignant tumours and would be useful for diagnosis of malignant tumours of the head and neck. However, further study would be required.
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Acknowledgements
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I wish to thank the late Professor Takenori Noikura for his help and I wish to pray for the repose of his soul. This evaluation was performed with the help of Grand-in-Aid for Science Research (C) (2), No. 13671972 in Japan.
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References
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Abstract
Introduction
